Malaria, a blood disease of humans, is responsible for 200 million cases annually. In Africa alone malaria is responsible for a million deaths. Eradication of the disease has failed, and the number of cases is increasing due to the appearance of parasite strains resistant to what were once effective antimalarials, the development of vector resistance to insecticides, the absence of an effective vaccine, and economic constraints. One logical approach toward providing effective chemoprophylaxis and treatment of malaria is to develop new drugs that specifically inhibit parasite growth and reproduction. Development of such a drug arsenal would be considerably facilitated by a more complete understanding of the biochemical differences that may exist between the intracellular plasmodium and its host. The proposed program of research is designed to provide such essential and basic information by studying: 1) the mechanisms of purine transport by the erythrocytic stages of the human malaria, Plasmodium falciparum; 2) the metabolic conversion of purines, nucleosides and nucleotides that take place both in the red cell and in the parasite during its development; 3) the purine salvage pathway enzymes of P. falciparum; 4) the possible role exogenous purine nucleobases and nucleosides may play in improving the in vitro growth of the parasites; and 5) the effect of anitmalarial drugs on parasite purine metabolism in vitro. Isotopic and enzymatic techniques, as well as high performance liquid chromatography, will be used to follow transport, changes in the purine pool, and metabolic pathways. In vitro cultures of the erythrocytic stages of p. falciparum will be maintained by the Trager-Jensen method.